慶應義塾研究者情報データベース

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• 私たちの免疫機能はゲノム配列の個人差（多型）によって規定されています。近年、特定の多型が免疫疾患の発症に関与することが明らかとなり、ゲノム研究による創薬（ゲノム創薬）が注目されています。しかし、免疫システムは非常に複雑であり、これらのリスク多型の免疫学的機能は解明されておらず、ゲノム創薬の成功例は少ないのが現状です。私たちの研究室は、ゲノム編集・シングルセル解析・マルチオミックスなどの最新の実験技術を活用して、免疫疾患のリスク多型の機能解明をとおして新しい創薬標的を同定することを目指しています。

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• Host Genetic Architecture between Epstein-Barr Virus Activity and Multiple Sclerosis Reveals Shared Pathways.

  Yasumizu Y, Kim N, Rivier CA, Moon J, Kojima S, Chen HL, Buitrago-Pocasangre N, Quinn E, Vaughn S, Morgan A, Huo S, Silberfeld A, Sumida TS, Ishigaki K, Longbrake EE, Falcone GJ, Hafler DA

  medRxiv : the preprint server for health sciences 2025年12月

  • Access to Document (DOI)

• The dynamic role of HLA proteins on compositional alterations of T-cell repertoires in inflammatory bowel disease

  2025年10月

  • Access to Document (DOI)

• Nonrandomized Allocation of Steroid Therapy in Patients With Fukuyama Congenital Muscular Dystrophy: Study Protocol for a Phase II Clinical Trial.

  Murakami T, Sato T, Ishizuka T, Nakamura H, Tachimori H, Harada H, Oi H, Hatano K, Oba MS, Ishiguro K, Shichiji M, Kihara Y, Takeshima Y, Taniguchi-Ikeda M, Hattori A, Shimizu-Motohashi Y, Awano H, Bo R, Nagata S, Ishigaki K

  Neuropsychopharmacology reports 45 （ 3 ） e70043 2025年09月

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• Tracking clonal dynamics of CD8 T cells and immune dysregulation in progression of systemic lupus erythematosus with nephritis

  Paek S.J., Lee H.S., Lee Y.J., Bang S.Y., Kim D., Kang B.K., Park D.J., Joo Y.B., Kim M., Kim H., Park S.Y., Park W.Y., Abe T., Itamiya T., Nagafuchi Y., Ishigaki K., Fujio K., Kim K.T., Bae S.C.

  Experimental and Molecular Medicine 57 （ 8 ） 1700 - 1710 2025年08月

  ISSN  12263613

  　概要を見る

  The fluctuating nature of disease activity in systemic lupus erythematosus (SLE), alternating between flares and remissions, poses substantial challenges for its effective management. The use of current biomarkers for monitoring SLE is limited in clinical settings owing to insufficient comprehension of the complex immune involvement underlying the disease course. Here, therefore, we profiled peripheral blood mononuclear cells at both stable and exacerbation states (total of n = 19) from six patients with SLE and 32 healthy donors using integrated single-cell RNA and T cell receptor (TCR) sequencing. To validate our findings, we analyzed two independent external datasets: bulk RNA sequencing and TCR data from 79 controls and 62 patients with SLE and single-cell RNA sequencing data from 99 healthy controls and 162 patients with SLE. Our analysis revealed cell type-specific activation of interferon-related genes in SLE grouped into four clusters, with elevated activity in disease-associated immune cells. Among these, atypical B cells associated with autoantibody production exhibited distinct differentiation patterns compared with conventional memory B cells, driven by heightened interferon signaling in SLE. Notably, clonal expansion of effector CD8 T cells emerged as a key driver of disease exacerbation, as indicated by reduced TCR diversity. Specific CD8 T cell clonotypes expanded during flare states, transitioning to effector phenotypes that exhibited heightened cytotoxicity and amplified interferon signaling, strongly correlating with tissue damage and flare severity. Our findings establish a critical link between interferon-driven mechanisms and cytotoxic T cell dysfunction in SLE flares, offering potential targets for therapeutic intervention and predictive biomarkers.

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• Accurate, sensitive, and efficient chromatin accessibility quantification at target loci using UNIChro-seq

  2025年07月

  　概要を見る

  <jats:title>Abstract</jats:title>
  <jats:p>Recent progress in statistical and experimental fine mapping of disease risk variants prompts us to focus on specific target loci for functional investigation. However, current genetics is hindered by a limited toolbox for target-loci analysis. To address this, we developed UNIChro-seq, a method that digitally counts accessible chromatin molecules at target loci. UNIChro-seq allows for accurate, sensitive, and efficient quantification of allelic effects compared to conventional methods. Using UNIChro-seq, we investigated the effects of 57 autoimmunity risk alleles on chromatin accessibility and estimated the causal effects of 20 artificial variants generated through genome editing. As a caveat, non-negligible fraction of the edited allele exhibited a falsely positive effect on chromatin accessibility, which can be effectively distinguished from the true causal effect through bi-directional genome editing. Finally, functional dissection of a fine-mapped risk variant at the <jats:italic>LEF1</jats:italic> locus illuminated its impact on T cell pathology in rheumatoid arthritis. Together, these findings underscore the utility of combining UNIChro-seq with genome editing technology to enable precise and scalable functional analysis of disease-associated loci.</jats:p>

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• Unveiling the dynamics of B lymphocytes in systemic lupus erythematosus patients treated with belimumab through longitudinal single-cell RNA sequencing (Jul, keae364, 2024)

  RHEUMATOLOGY  2025年

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• Big Data Science on T Cell Receptor-mediated Immune Regulation

  Ishigaki K

  JMA JOURNAL 8 （ 2 ） 338 - 344 2025年

  ISSN  2433-328X

  • Access to Document (DOI)

• Correction to: Interferon subverts an AHR–JUN axis to promote CXCL13+ T cells in lupus (Nature, (2024), 631, 8022, (857-866), 10.1038/s41586-024-07627-2)

  Law C., Wacleche V.S., Cao Y., Pillai A., Sowerby J., Hancock B., Horisberger A., Bracero S., Skidanova V., Li Z., Adejoorin I., Dillon E., Benque I.J., Nunez D.P., Simmons D.P., Keegan J., Chen L., Baker T., Brohawn P.Z., Al-Mossawi H., Hao L.Y., Jones B., Rao N., Qu Y., Alves S.E., Wyse A., Cordle A., Zhu Z., Zhang F., Xiao Q., Weisman M., Weisenfeld D., Weinand K., Wei K., Watts G.F.M., Utz P.J., Tabechian D., Smith M., Slowikowski K., Singaraju A., Scheel-Toellner D., Seifert J.A., Sakaue S., Sahbudin I., Rumker L., Robinson W.H., Rivellese F., Ritchlin C., Reshef Y., Raza K., Raychaudhuri S., Rangel-Moreno J., Pitzalis C., Perlman H., Orange D.E., Nerviani A., Nayar S., Moreland L., Millard N., Meednu N., Mears J.R., McGeachy M.J., McDavid A., Maybury M., Marks K.E., Mantel I., Mandelin A.M., Liao K., Li Y., Lewis M.J., Lederer J.A., Lakhanpal A., Korsunsky I., Keras G., Kang J.B., Jonsson A.H., James J.A., Ishigaki K., Ivashkiv L.B., Hughes L.B., Horowitz D., Holers V.M., Gutierrez-Arcelus M., Guthridge J.M., Gregersen P.K., Gravallese E.M., Goodman S.M., Geraldino-Pardilla L., Forbess L., Firestein G.S., Carr H., Filer A., Dunn P., Donlin L.T., DiCarlo E., Deane K.D., Curtis M., Chicoine A., Ceponis A., Campbell D.

  Nature 632 （ 8025 ）  2024年08月

  ISSN  00280836

  　概要を見る

  In the version of the article initially published, in Fig. 2j, the x-axis labels “AHRinh” and “TCDD” (now middle and right) were switched and have now been corrected in the HTML and PDF versions of the article.

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• Erratum: Identification of a regulatory pathway governing TRAF1 via an arthritis-associated non-coding variant (Cell Genomics (2023) 3(11), (S2666979X2300246X), (10.1016/j.xgen.2023.100420))

  Wang Q., Martínez-Bonet M., Kim T., Sparks J.A., Ishigaki K., Chen X., Sudman M., Aguiar V., Sim S., Hernandez M.C., Chiu D.J., Wactor A., Wauford B., Marion M.C., Gutierrez-Arcelus M., Bowes J., Eyre S., Nordal E., Prahalad S., Rygg M., Videm V., Raychaudhuri S., Weirauch M.T., Langefeld C.D., Thompson S.D., Nigrovic P.A.

  Cell Genomics 4 （ 2 ）  2024年02月

  　概要を見る

  (Cell Genomics 3, 100420; November 8, 2023) Figures 4D, 4E, and 4F were inadvertently omitted from the graphic in the initial publication. The figure has now been corrected in the online article. The authors apologize for the error. [Formula presented] [Formula presented]

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• Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses

  Shiraishi K., Takahashi A., Momozawa Y., Daigo Y., Kaneko S., Kawaguchi T., Kunitoh H., Matsumoto S., Horinouchi H., Goto A., Honda T., Shimizu K., Torasawa M., Takayanagi D., Saito M., Saito A., Ohe Y., Watanabe S.i., Goto K., Tsuboi M., Tsuchihara K., Takata S., Aoi T., Takano A., Kobayashi M., Miyagi Y., Tanaka K., Suzuki H., Maeda D., Yamaura T., Matsuda M., Shimada Y., Mizuno T., Sakamoto H., Yoshida T., Goto Y., Yoshida T., Yamaji T., Sonobe M., Toyooka S., Yoneda K., Masago K., Tanaka F., Hara M., Fuse N., Nishizuka S.S., Motoi N., Sawada N., Nishida Y., Kumada K., Takeuchi K., Tanno K., Yatabe Y., Sunami K., Hishida T., Miyazaki Y., Ito H., Amemiya M., Totsuka H., Nakayama H., Yokose T., Ishigaki K., Nagashima T., Ohtaki Y., Imai K., Takasawa K., Minamiya Y., Kobayashi K., Okubo K., Wakai K., Shimizu A., Yamamoto M., Iwasaki M., Matsuda K., Inazawa J., Shiraishi Y., Nishikawa H., Murakami Y., Kubo M., Matsuda F., Kamatani Y., Hamamoto R., Matsuo K., Kohno T.

  Cancer Communications 44 （ 2 ） 287 - 293 2024年02月

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担当授業科目 【 表示 ／ 非表示 】

担当授業科目 【 表示 ／ 非表示 】

• 微生物学・免疫学特論

  2025年度

• 症例検討

  2025年度

• 免疫学

  2025年度

• 基礎臨床統合医学

  2025年度

• 微生物学・免疫学

  2025年度

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